Yang Jialu, Xu Huimin, Zhao Yijun, Sun Pengju, Li Yuanyuan, Chen Ting, Zhou Yanmei
State Key Laboratory of Antiviral Drugs, Henan Joint International Research Laboratory of Environmental Pollution Control Materials, College of Chemistry and Molecular Sciences, Henan University, Kaifeng, 475004, China.
Department of General Medicine, Huaihe Hospital, Henan University, Kaifeng, 475000, China.
Biosens Bioelectron. 2025 Feb 1;269:116967. doi: 10.1016/j.bios.2024.116967. Epub 2024 Nov 25.
Non-alcoholic fatty liver disease (NAFLD) has evolved to become a major cause of hepatocellular carcinoma (HCC). Visualization of NAFLD-HCC deterioration process imaging is essential to understand the underlying pathophysiological processes. However, currently relevant probes with short emission wavelengths, univariate and the inability to achieve theranostics functionality have encountered obstacles in further evaluating the NAFLD-HCC process. Here, we present a carboxylesterase (CE)-activated NIR fluorescent probe (BODJ) which has lipid droplets (LDs)-targeting ability and emits at a wavelength of 858 nm with a fluorescence quantum yield of 19.06%. CE-activated BODJ was used as a visual tool to successfully visualize both NAFLD deterioration processes and HCC in situ based on changes in the average number of LDs and the associated fluorescence intensity fluctuations. Imaging results showed that changes associated with CE and LDs in the modelled cells varied during the transition from nonalcoholic fatty liver to nonalcoholic steatohepatitis and later progression to HCC, highlighting the close association between bivariate and disease. We also demonstrate that BODJ has photodynamic (PDT) and photothermal therapy (PTT) capabilities, allowing image-guided dual phototherapy to damage HCC in situ. This NIR probe, which takes advantage of bivariate to track the deterioration process that illuminates NAFLD-HCC and has dual phototherapy capabilities, provides new ideas for the design of probes related to the diagnosis and treatment of hepatic metabolic diseases.
非酒精性脂肪性肝病（NAFLD）已演变成肝细胞癌（HCC）的主要病因。可视化NAFLD - HCC的恶化过程成像对于理解潜在的病理生理过程至关重要。然而，目前相关探针存在发射波长较短、单变量以及无法实现诊疗功能等问题，在进一步评估NAFLD - HCC过程中遇到了障碍。在此，我们展示了一种羧酸酯酶（CE）激活的近红外荧光探针（BODJ），它具有靶向脂滴（LDs）的能力，发射波长为858 nm，荧光量子产率为19.06%。基于LDs平均数量的变化和相关荧光强度波动，CE激活的BODJ被用作可视化工具，成功地原位可视化了NAFLD的恶化过程和HCC。成像结果表明，在从非酒精性脂肪肝转变为非酒精性脂肪性肝炎以及随后进展为HCC的过程中，模型细胞中与CE和LDs相关的变化各不相同，突出了双变量与疾病之间的紧密关联。我们还证明BODJ具有光动力（PDT）和光热疗法（PTT）能力，允许进行图像引导的双重光疗以原位损伤HCC。这种利用双变量追踪阐明NAFLD - HCC的恶化过程并具有双重光疗能力的近红外探针，为肝代谢疾病诊断和治疗相关探针的设计提供了新思路。
